Eörs Szathmáry
Collegium Budapest, Hungary, and The Parmenides Foundation for the Study of Thinking, Munich, Germany
A theoretical biologist recommends thought-provoking reading on the origin of translation and the genetic code.
As Francis Crick and his co-workers once noted, "the origin of protein synthesis is a notoriously difficult problem". Our best hopes of resolving this problem begin, in my opinion, in an RNA world.
The RNA-world hypothesis holds that RNA emerged before DNA and proteins, neatly separating the origin of life from that of the genetic code and its translation. The question then becomes: how did RNA evolve to make proteins?
In a recent paper, Yuri Wolf and Eugene Koonin of the National Institutes of Health in Bethesda, Maryland, present one scenario (Biol. Direct 2, 14; 2007).
They rightly call attention to studies that suggest that protein-based aminoacyl-tRNA synthetases, which are involved in the first steps of assembling amino acids into proteins, are relatively late evolutionary inventions. This forces us to accept the idea that protein synthesis is older than such synthetases.
Before the evolution of synthetases, the only agents that could conceivably have marshalled amino acids are RNA enzymes, or ribozymes. Wolf and Koonin share my view that the recruitment of amino acids was driven by selection for enhanced catalytic activity, and that the ancestor of the large ribosomal RNA that catalyses protein synthesis in today's cells — a molecular 'fossil' — was a catalyst that linked only two amino acids.
I am less happy with these authors' suggestion of a relatively late switch from peptide-specific proto-ribosomes to those that could use an external template such as mRNA to synthesize peptides with arbitrary sequence — but they may well be right.
They lay out an evolutionary sequence that is more complete than the scenario I once proposed. I highly recommend this well-written, thought-provoking paper.
Comments
SIR- The origin of translation must have required a reliable source of s-adenosylmethionine (SAM) for universal methylation of the 3'-terminal segment of 16S rRNA and guanosine in position 37 of tRNA, both of which are required for protein synthesis. (The oldest known ribonucleotide reductase also requires SAM as a cofactor.) However, I have been unable to find any work suggesting that an early RNA polymer randomly acquired the ability to synthesize SAM or to catalyze methyltransferase reactions. Might this capability have protected polymers from degradation by ribonuclease P and greatly improved thier propensity to form other structures advantgeous for catalysis? Might this mechanism help explain how RNA evolved to make proteins? Moreover, considering the importance of SAM in regulating global gene expression, might this capability still be found in modern biological systems?
Posted by: Seth Woodruff | October 4, 2007 09:44 AM
BioMed Central, which publishes the journal Biology Direct, have flagged this column on their blog here.
Posted by: Jenny Hogan | October 4, 2007 10:19 AM
Wolf and Koonin provide a thought provoking contribution to the question of how protein synthesis may have originated.
I agree with the assumptions and premises of their model with one exception. This is their statement, under heading 4, "In principle, it is possible to imagine that the primordial translation system included a complement of proteins distinct from the modern one however this hypothesis not only has no empirical support but also leads to infinite regression". The gist of this sentence is repeated in their Discussion and Conclusion.
I have previously proposed a model for the origin of translation which involved the production of proteins by a primitive, intermediate, translation mechanism. (Polynucleotide Replication Coupled to Protein Synthesis: a Possible Mechanism for the Origin of Life. Orig. Life 12 (1982) 55-69). I still think this model is plausible and deserves consideration. In this model I proposed that primitive tRNA molecules condensed to form poly-tRNAs. Replication of the poly-tRNAs by stepwise incorporation of primitive aminoacylated tRNAs was accompanied by growth of a peptide chain in a manner similar to that of modern protein synthesis. The distinguishing feature of this mechanism is that the peptide chain grows by a single amino acid for each tRNA incorporated into poly-tRNA. It appears that this mechanism might have the capacity to evolve into triplet-coded protein synthesis if a subset of poly-tRNAs, together with proteins encoded by poly-tRNAs, evolved a structure similar in function to the modern ribosome (see Fig.6 in my paper).
I see two major advantages of this model. Firstly, tRNAs, or something similar, which must have been present at early times, are central to the proposed mechanism of primitive protein synthesis. Secondly, because protein synthesis and replication are coupled, continued synthesis is assured of any useful proteins. Wolf and Koonin are not very explicit as to how replication of the critical components of their model is ensured.
Finally, I suggested that when triplet-coded protein synthesis evolved, both it and the primitive mechanism would have functioned together until the superior coding capacity of the modern mechanism supplanted the primitive version. Any model for the origin of translation that relies on the activities of the RNA world must require that, as proteins take over the role of ribozymes, both would function together. So there does not seem to be any overwhelming reason why a primitive protein synthesis system could not function along with the modern mechanism until the latter rendered the former superfluous.
The Wolf and Koonin model supplies a quite detailed account of the origin of translation and relies primarily on steps that involve ribozymal RNAs alone. This may well be the correct scenario. However, if we admit a role for a primitive precursor mechanism of protein synthesis, it seems to me that this greatly simplifies the problem of the origin of translation. I still prefer my model - as one does.
Posted by: Tony Mackinlay | November 13, 2007 01:04 PM